The objectives of this project are to (1) use recombinant DNA techniques to express specific antigens of Borrelia burgdorferi to improve the serodiagnosis of Lyme disease, (2) characterize at the molecular level, isolates of the Lyme disease spirochete from a wide range of biological and geographical sources, and (3) to use animal models to help understand the pathogenesis of Lyme disease and to examine serological responses to infection. During the last year we entered into a collaboration with Korean scientists to examine the potential for human Lyme disease in Korea. Lyme disease spirochetes, Borrelia burgdorferi sensu lato, were identified and characterized for the first time from Korea. Four isolates, designated Konkuk-1, Konkuk-2, Kangwon-3, and KM-4 were made from midgut suspensions of three Ixodes ticks and heart tissue from one mouse, Apodemus agrarius, collected from Chungbuk and Kangwon Provinces. The four Korean isolates and B. burgdorferi sensu lato from other geographic areas and biological sources were compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for protein profiles, Western immunoblot analysis for reactivities with monoclonal and polyclonal antibodies, and agarose gel electrophoresis for plasmid profiles. Two typing schemes using the polymerase chain reaction (PCR) identified three of the isolates as members of group VS461 and one, Kangwon-3, as B. garinii. These results demonstrate the potential for human Lyme disease to occur in some provinces of Korea. Previous studies have demonstrated that the urinary bladder is a consistent source for isolating the Lyme disease spirochete, Borrelia burgdorferi, from both experimentally infected and naturally exposed rodents. We examined histopathological changes in the urinary bladder of different types of rodents experimentally infected with Lyme spirochetes, including BALB/c mice (Mus musculus), nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and grasshopper mice (Onychomys leucogaster). Animals were inoculated intraperitoneally, subcutaneously, or intranasally with low-passaged spirochetes, high- passaged spirochetes, or phosphate-buffered saline. At various times following inoculation, animals were sacrificed and approximately one-half of each urinary bladder and kidney were cultured separately in BSK-II medium while the other half of each organ was prepared for histological examination. Spirochetes were cultured from the urinary bladder of all 35 mice inoculated with low-passaged spirochetes while we were unable to isolate spirochetes from any kidneys of the same mice. The pathological changes observed most frequently in the urinary bladder of the infected mice were the presence of lymphoid aggregates, vascular changes including an increase in the number of vessels and thickening of the vessel walls, and perivascular infiltrates. Our results demonstrate that nearly all individuals (93%) of the four types of mice examined had a cystitis associated with spirochetal infection.